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铜/钆共掺杂羟基磷灰石/聚乳酸-羟基乙酸共聚物复合材料增强磁共振成像及骨缺损再生能力。

Cu/Gd co-doped hydroxyapatite/poly lactic-co-glycolic acid composites enhance MRI imaging and bone defect regeneration.

作者信息

Lu Wei, Xia Xin, Ma Yihang, He Hongtao, Kikkawa Don O, Zhang Lu, Zhang Bo, Liu Xiangji

机构信息

Department of orthopedics, Digital orthopedic laboratory, The Second Hospital of Dalian Medical University, Dalian, P. R. China.

Department of Spine Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.

出版信息

J Biomater Appl. 2025 Jan;39(6):632-647. doi: 10.1177/08853282241276064. Epub 2024 Sep 8.

Abstract

The hydroxyapatite (HA)/poly(lactide-co-glycolide) acid (PLGA) composite material is a widely used orthopedic implant due to its excellent biocompatibility and plasticity. Recent advancements in cation doping have expanded its potential biological applications. However, conventional HA/PLGA composites are not visible under X-rays post-implantation and have limited osteogenic induction capabilities. Copper (Cu) is known to regulate osteoblast proliferation and differentiation, while gadolinium (Gd) can significantly enhance the magnetic resonance imaging (MRI) capabilities of materials. This study aimed to investigate whether incorporating Cu and Gd into an HA/PLGA composite could enhance the osteogenic properties, in vivo bone defect repair, and MRI characteristics. We prepared a Cu/Gd@HA/PLGA composite and assessed its performance. Material characterization confirmed that Cu/Gd@HA retained the morphology and crystal structure of HA. The Cu/Gd@HA/PLGA composite exhibited excellent nuclear magnetic imaging capabilities, porosity, and hydrophilicity, which are conducive to cell adhesion and implant detection. In vitro experiments demonstrated that the Cu/Gd@HA/PLGA composite enhanced the proliferation, differentiation, and adhesion of MC3T3-E1 cells, and upregulated COL-1 and BMP-2 expression at both gene and protein levels. In vivo studies showed that the Cu/Gd@HA/PLGA composite maintained strong T1-weighted MRI signals and significantly improved the bone defect healing rate in rats. These findings indicate that the Cu/Gd@HA/PLGA composites significantly enhance T1-weighted MRI capabilities, promote osteoblast proliferation and differentiation in vitro, and accelerate bone defect healing in vivo.

摘要

羟基磷灰石(HA)/聚(丙交酯-乙交酯)酸(PLGA)复合材料因其优异的生物相容性和可塑性而成为广泛应用的骨科植入物。阳离子掺杂的最新进展扩展了其潜在的生物学应用。然而,传统的HA/PLGA复合材料在植入后X射线下不可见,且成骨诱导能力有限。已知铜(Cu)可调节成骨细胞的增殖和分化,而钆(Gd)可显著增强材料的磁共振成像(MRI)能力。本研究旨在探讨将Cu和Gd掺入HA/PLGA复合材料中是否能增强其成骨特性、体内骨缺损修复能力和MRI特性。我们制备了Cu/Gd@HA/PLGA复合材料并评估了其性能。材料表征证实Cu/Gd@HA保留了HA的形态和晶体结构。Cu/Gd@HA/PLGA复合材料表现出优异的核磁共振成像能力、孔隙率和亲水性,有利于细胞粘附和植入物检测。体外实验表明,Cu/Gd@HA/PLGA复合材料增强了MC3T3-E1细胞的增殖、分化和粘附,并在基因和蛋白质水平上调了COL-1和BMP-2的表达。体内研究表明,Cu/Gd@HA/PLGA复合材料保持了较强的T1加权MRI信号,并显著提高了大鼠骨缺损的愈合率。这些发现表明,Cu/Gd@HA/PLGA复合材料显著增强了T1加权MRI能力,促进了体外成骨细胞的增殖和分化,并加速了体内骨缺损的愈合。

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